ID   TSN5_HUMAN              Reviewed;         268 AA.
AC   P62079; B2RDY2; O60628; O60746; Q6FHE5; Q9JLY1;
DT   21-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT   21-JUN-2004, sequence version 1.
DT   04-NOV-2026, entry version 153.
DE   RecName: Full=Tetraspanin-5;
DE            Short=Tspan-5;
DE   AltName: Full=Tetraspan NET-4;
DE   AltName: Full=Transmembrane 4 superfamily member 9;
GN   Name=TSPAN5 {ECO:0000312|HGNC:HGNC:17753}; Synonyms=TM4SF9;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=9714763; DOI=10.1016/s0167-4781(98)00087-6;
RA   Todd S.C., Doctor V.S., Levy S.;
RT   "Sequences and expression of six new members of the tetraspanin/TM4SF
RT   family.";
RL   Biochim. Biophys. Acta 1399:101-104(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Rubinstein E., Serru V., Boucheix C.;
RT   "New tetraspans identified in the EST database.";
RL   Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA   Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P.,
RA   Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y.,
RA   LaBaer J.;
RT   "Cloning of human full open reading frames in Gateway(TM) system entry
RT   vector (pDONR201).";
RL   Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Testis;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Pancreas;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [7]
RP   FUNCTION, INTERACTION WITH ADAM10, AND SUBCELLULAR LOCATION.
RX   PubMed=26686862; DOI=10.1007/s00018-015-2111-z;
RA   Jouannet S., Saint-Pol J., Fernandez L., Nguyen V., Charrin S.,
RA   Boucheix C., Brou C., Milhiet P.E., Rubinstein E.;
RT   "TspanC8 tetraspanins differentially regulate the cleavage of ADAM10
RT   substrates, Notch activation and ADAM10 membrane compartmentalization.";
RL   Cell. Mol. Life Sci. 73:1895-1915(2016).
RN   [8]
RP   FUNCTION.
RX   PubMed=28600292; DOI=10.4049/jimmunol.1600713;
RA   Reyat J.S., Chimen M., Noy P.J., Szyroka J., Rainger G.E., Tomlinson M.G.;
RT   "ADAM10-Interacting Tetraspanins Tspan5 and Tspan17 Regulate VE-Cadherin
RT   Expression and Promote T Lymphocyte Transmigration.";
RL   J. Immunol. 199:666-676(2017).
RN   [9]
RP   FUNCTION, INTERACTION WITH ADAM10, SUBCELLULAR LOCATION, AND
RP   PALMITOYLATION.
RX   PubMed=31792032; DOI=10.26508/lsa.201900444;
RA   Eschenbrenner E., Jouannet S., Clay D., Chaker J., Boucheix C., Brou C.,
RA   Tomlinson M.G., Charrin S., Rubinstein E.;
RT   "TspanC8 tetraspanins differentially regulate ADAM10 endocytosis and half-
RT   life.";
RL   Life Sci. Alliance 3:0-0(2020).
RN   [10]
RP   FUNCTION.
RX   PubMed=37516108; DOI=10.1016/j.cell.2023.06.026;
RA   Lipper C.H., Egan E.D., Gabriel K.H., Blacklow S.C.;
RT   "Structural basis for membrane-proximal proteolysis of substrates by
RT   ADAM10.";
RL   Cell 186:3632-3641.e10(2023).
CC   -!- FUNCTION: Part of TspanC8 subgroup, composed of 6 members that interact
CC       with the transmembrane metalloprotease ADAM10. This interaction is
CC       required for ADAM10 exit from the endoplasmic reticulum and for
CC       enzymatic maturation and trafficking to the cell surface as well as
CC       substrate specificity. Different TspanC8/ADAM10 complexes have distinct
CC       substrates (PubMed:26686862, PubMed:28600292, PubMed:37516108).
CC       Promotes ADAM10-mediated cleavage of CD44 (PubMed:26686862). Seems to
CC       regulate VE-cadherin expression in endothelial cells probably through
CC       interaction with ADAM10, promoting leukocyte transmigration
CC       (PubMed:28600292). {ECO:0000269|PubMed:26686862,
CC       ECO:0000269|PubMed:28600292, ECO:0000269|PubMed:37516108}.
CC   -!- SUBUNIT: Interacts with ADAM10; the interaction influences ADAM10
CC       substrate specificity, endocytosis and turnover.
CC       {ECO:0000269|PubMed:26686862, ECO:0000269|PubMed:31792032}.
CC   -!- INTERACTION:
CC       P62079; O14672: ADAM10; NbExp=12; IntAct=EBI-20977525, EBI-1536151;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:26686862,
CC       ECO:0000269|PubMed:31792032}; Multi-pass membrane protein
CC       {ECO:0000305}.
CC   -!- PTM: Palmitoylated. {ECO:0000269|PubMed:31792032}.
CC   -!- SIMILARITY: Belongs to the tetraspanin (TM4SF) family. {ECO:0000305}.
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DR   EMBL; AF053455; AAC69712.1; -; Genomic_DNA.
DR   EMBL; AF065389; AAC17120.1; -; mRNA.
DR   EMBL; CR541809; CAG46608.1; -; mRNA.
DR   EMBL; AK315723; BAG38079.1; -; mRNA.
DR   EMBL; CH471057; EAX06074.1; -; Genomic_DNA.
DR   EMBL; BC009704; AAH09704.1; -; mRNA.
DR   CCDS; CCDS3646.1; -.
DR   PIR; A59261; A59261.
DR   RefSeq; NP_005714.2; NM_005723.4.
DR   AlphaFoldDB; P62079; -.
DR   SMR; P62079; -.
DR   BioGRID; 115405; 85.
DR   FunCoup; P62079; 589.
DR   IntAct; P62079; 102.
DR   STRING; 9606.ENSP00000307701; -.
DR   GlyCosmos; P62079; 4 sites, No reported glycans.
DR   GlyGen; P62079; 4 sites.
DR   iPTMnet; P62079; -.
DR   PhosphoSitePlus; P62079; -.
DR   SwissPalm; P62079; -.
DR   BioMuta; TSPAN5; -.
DR   DMDM; 49065848; -.
DR   jPOST; P62079; -.
DR   MassIVE; P62079; -.
DR   PaxDb; 9606-ENSP00000307701; -.
DR   PeptideAtlas; P62079; -.
DR   ProteomicsDB; 57363; -.
DR   Antibodypedia; 25821; 185 antibodies from 29 providers.
DR   DNASU; 10098; -.
DR   Ensembl; ENST00000305798.8; ENSP00000307701.3; ENSG00000168785.9.
DR   GeneID; 10098; -.
DR   KEGG; hsa:10098; -.
DR   MANE-Select; ENST00000305798.8; ENSP00000307701.3; NM_005723.4; NP_005714.2.
DR   UCSC; uc003hub.4; human.
DR   AGR; HGNC:17753; -.
DR   ClinPGx; PA134864098; -.
DR   CTD; 10098; -.
DR   DisGeNET; 10098; -.
DR   GeneCards; TSPAN5; -.
DR   HGNC; HGNC:17753; TSPAN5.
DR   HPA; ENSG00000168785; Tissue enhanced (brain).
DR   MalaCards; TSPAN5; -.
DR   MIM; 613136; gene.
DR   OpenTargets; ENSG00000168785; -.
DR   VEuPathDB; HostDB:ENSG00000168785; -.
DR   eggNOG; KOG3882; Eukaryota.
DR   GeneTree; ENSGT00940000161376; -.
DR   HOGENOM; CLU_055524_0_2_1; -.
DR   InParanoid; P62079; -.
DR   OMA; ACGYAGP; -.
DR   OrthoDB; 2014092at2759; -.
DR   PAN-GO; P62079; 1 GO annotation based on evolutionary models.
DR   PhylomeDB; P62079; -.
DR   PathwayCommons; P62079; -.
DR   Reactome; R-HSA-977225; Amyloid fiber formation.
DR   SignaLink; P62079; -.
DR   Agora; ENSG00000168785; -.
DR   BioGRID-ORCS; 10098; 11 hits in 1152 CRISPR screens.
DR   ChiTaRS; TSPAN5; human.
DR   GenomeRNAi; 10098; -.
DR   Pharos; P62079; Tbio.
DR   PRO; PR:P62079; -.
DR   Proteomes; UP000005640; Chromosome 4.
DR   RNAct; P62079; protein.
DR   Bgee; ENSG00000168785; Expressed in secondary oocyte and 192 other cell types or tissues.
DR   ExpressionAtlas; P62079; baseline and differential.
DR   GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR   GO; GO:0045747; P:positive regulation of Notch signaling pathway; IMP:UniProtKB.
DR   GO; GO:0072659; P:protein localization to plasma membrane; IMP:UniProtKB.
DR   GO; GO:0051604; P:protein maturation; IMP:UniProtKB.
DR   GO; GO:0051043; P:regulation of membrane protein ectodomain proteolysis; IDA:UniProtKB.
DR   CDD; cd03159; TM4SF9_like_LEL; 1.
DR   FunFam; 1.10.1450.10:FF:000001; Tetraspanin; 1.
DR   Gene3D; 1.10.1450.10; Tetraspanin; 1.
DR   InterPro; IPR018499; Tetraspanin/Peripherin.
DR   InterPro; IPR000301; Tetraspanin_animals.
DR   InterPro; IPR018503; Tetraspanin_CS.
DR   InterPro; IPR008952; Tetraspanin_EC2_sf.
DR   PANTHER; PTHR19282; TETRASPANIN; 1.
DR   PANTHER; PTHR19282:SF63; TETRASPANIN-5; 1.
DR   Pfam; PF00335; Tetraspanin; 1.
DR   PIRSF; PIRSF002419; Tetraspanin; 1.
DR   PRINTS; PR00259; TMFOUR.
DR   SUPFAM; SSF48652; Tetraspanin; 1.
DR   PROSITE; PS00421; TM4_1; 1.
PE   1: Evidence at protein level;
KW   Cell membrane; Disulfide bond; Glycoprotein; Membrane;
KW   Proteomics identification; Reference proteome; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..268
FT                   /note="Tetraspanin-5"
FT                   /id="PRO_0000219243"
FT   TOPO_DOM        1..17
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        18..38
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        39..61
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        62..82
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        83..92
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        93..113
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        114..232
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        233..253
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        254..268
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        49
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        169
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        174
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        232
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        153..221
FT                   /evidence="ECO:0000250|UniProtKB:O95858"
FT   DISULFID        154..186
FT                   /evidence="ECO:0000250|UniProtKB:O95858"
FT   DISULFID        170..180
FT                   /evidence="ECO:0000250|UniProtKB:O95858"
FT   DISULFID        187..200
FT                   /evidence="ECO:0000250|UniProtKB:O95858"
FT   CONFLICT        91..94
FT                   /note="Missing (in Ref. 1; AAC69712)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   268 AA;  30337 MW;  7F4480BD0FA6192D CRC64;
     MSGKHYKGPE VSCCIKYFIF GFNVIFWFLG ITFLGIGLWA WNEKGVLSNI SSITDLGGFD
     PVWLFLVVGG VMFILGFAGC IGALRENTFL LKFFSVFLGI IFFLELTAGV LAFVFKDWIK
     DQLYFFINNN IRAYRDDIDL QNLIDFTQEY WQCCGAFGAD DWNLNIYFNC TDSNASRERC
     GVPFSCCTKD PAEDVINTQC GYDARQKPEV DQQIVIYTKG CVPQFEKWLQ DNLTIVAGIF
     IGIALLQIFG ICLAQNLVSD IEAVRASW
//